Kinetic studies of bioactive products nitric oxide and 8-iso-PGF_2αinBurkholderia pseudomalleiinfected human macrophages, and their role in the intracellular survival of these organisms

Abstract

The oxidative response of Burkholderia pseudomallei and Escherichia coli infected macrophages from normal and melioidosis subjects was determined by measuring the production of nitric oxide which is one of the reactive nitrogen intermediates, and the activation state of these macrophages was determined by measuring the generation of 8-iso-PGF(2alpha), a bioactive product of free radical induced lipid peroxidation. Macrophages obtained from the melioidosis patients generated significantly lower levels of nitric oxide and 8-iso-PGF(2alpha) compared to macrophages obtained from the normal subjects (P<0.001). The reduced efficiency of the oxygen dependent microbicidal mechanism in macrophages of melioidosis patients may be one of the survival strategies developed by B. pseudomallei to remain viable intracellularly.

Quorum sensing regulates dpsA and the oxidative stress response in Burkholderia pseudomallei

“…pseudomallei can resist phagocytic intracellular killing (Egan & Gordon, 1996) and remain dormant within a host for many years (Nathan et al, 2005). It has evolved a variety of mechanisms to protect its DNA from oxidative damage from either cellular metabolism or the environment, and under such conditions will produce high levels of the nonspecific DNA-binding protein DpsA, which effectively Fig.…”

Why is the response rate slow in ceftazidime therapy for melioidosis?

“…In monocytes from patients with diabetes, after internalization of B. pseudomallei, phagolysosome formation occurred slowly and inefficiently, leading to an increased number of intracellular organisms compared with monocytes obtained from healthy blood donors [10]. In addition, the respiratory burst, which is cytotoxic and inhibits replication of intracellular organisms, was also impaired in such patients [11]. Besides diabetes there are many other predisposing risk factors for melioidosis.…”